Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD) and its involvement in the biosynthesis of epitestosterone
Open accessAbstract
BACKGROUND: Epi-testosterone (epiT) is the 17alpha-epimer of testosterone. It has been found at similar level as testosterone in human biological fluids. This steroid has thus been used as a natural internal standard for assessing testosterone abuse in sports. EpiT has been also shown to accumulate in mammary cyst fluid and in human prostate. It was found to possess antiandrogenic activity as well as neuroprotective effects. So far, the exact pathway leading to the formation of epiT has not been elucidated. RESULTS: In this report, we describe the isolation and characterization of the enzyme 17alpha-hydroxysteroid dehydrogenase. The name is given according to its most potent activity. Using cells stably expressing the enzyme, we show that 17alpha-HSD catalyzes efficienty the transformation of 4-androstenedione (4-dione), dehydroepiandrosterone (DHEA), 5alpha-androstane-3,17-dione (5alpha-dione) and androsterone (ADT) into their corresponding 17alpha-hydroxy-steroids : epiT, 5-androstene-3beta,17alpha-diol (epi5diol), 5alpha-androstane-17alpha-ol-3-one (epiDHT) and 5alpha-androstane-3alpha,17alpha-diol (epi3alpha-diol), respectively. Similar to other members of the aldo-keto reductase family that possess the ability to reduce the keto-group into hydroxyl-group at different position on the steroid nucleus, 17alpha-HSD could also catalyze the transformation of DHT, 5alpha-dione, and 5alpha-pregnane-3,20-dione (DHP) into 3alpha-diol, ADT and 5alpha-pregnane-3alpha-ol-20-one (allopregnanolone) through its less potent 3alpha-HSD activity. We also have over-expressed the 17alpha-HSD in Escherichia coli and have purified it by affinity chromatography. The purified enzyme exhibits the same catalytic properties that have been observed with cultured HEK-293 stably transfected cells. Using quantitative Realtime-PCR to study tissue distribution of this enzyme in the mouse, we observed that it is expressed at very high levels in the kidney. CONCLUSION: The present study permits to clarify the biosynthesis pathway of epiT. It also offers the opportunity to study gene regulation and function of this enzyme. Further study in human will allow a better comprehension about the use of epiT in drug abuse testing; it will also help to clarify the importance of its accumulation in breast cyst fluid and prostate, as well as its potential role as natural antiandrogen.
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A reductive 17αHSD (product of AKR1C21) has been isolated from the mouse and has been shown to convert 17-keto steroids to their 17α-hydroxyl.
“a reductive 17αHSD (product of AKR1C21) has been isolated from the mouse and has been shown to convert 17-keto steroids to their 17α-hydroxyl, thus suggesting that A4 could be the direct precursor to EpiT.”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Bellemare et al., 2005
This enzyme was specifically expressed in the mouse kidney.
“This enzyme was specifically expressed in the mouse kidney (Bellemare et al., 2005).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Bellemare et al., 2005
A4 could be the direct precursor to EpiT.
“thus suggesting that A4 could be the direct precursor to EpiT.”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Bellemare et al., 2005
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- Authors
- Bellemare, V., Faucher, F., Breton, R., & Luu-The, V.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Luu-The, Van
- ORCID
- Bellemare, Véronique
- Venue
- BMC Biochemistry
- Published
- 2005-07-14
- Volume
- 6
- Issue
- 1
- Pages
- 12-12
- ISSN
- 1471-2091 (ISSN-L)
- OpenAlex
- W1849642335
- Cited by
- 37
- References
- 31
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- BMC Biochemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- 3α-hydroxysteroid dehydrogenase, steroid metabolism, 4-androstenedione, dehydroepiandrosterone, androstanediol, allopregnanolone, enzyme purification, tissue distribution, kidney
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Enzyme Activation, Epitestosterone, Female, Humans, Hydroxysteroid Dehydrogenases, Male, Mice, Inbred C57BL, Molecular Sequence Data, Mice
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